FDA reviews Amgen’s prostate cancer drug Xgeva

By Dr. Ananya Mandal, MDFeb 7 2012

U.S. Food and Drug Administration (FDA) researchers say that an Amgen drug slowed the spread of cancer to the bone in men with hard-to-treat prostate cancer, though the drug did not extend life and carried significant side effects.

The FDA will next ask a panel of outside experts on Wednesday whether the benefits of Amgen’s Xgeva - chemically known as denosumab, outweigh its risks, which included bone disease in about 5 percent of patients taking the drug. The agency posted its review of the drug online Monday morning ahead of the meeting.

Xgeva is already approved for preventing fractures in cancerous bones, and for osteoporosis, in a different formulation called Prolia. Amgen has now put in its applications for approval of the injectable drug as a preventive measure for men with recurring prostate cancer that is at high risk of spreading to the bone. Men must have also attempted and failed treatment with hormone therapy.

A 1,432-patient study conducted by Amgen showed the drug slowed the spread of cancer to the bone by about 4.2 months when compared to patients who received placebo. While that delay was statistically significant, the FDA’s reviewers questioned whether it is “an adequate measure of clinical benefit” for patients with prostate cancer. FDA’s review notes that the drug did not increase overall survival, with patients in the drug and placebo groups living about the same amount of time. Additionally, five percent of patients taking Xgeva experienced the side effect of osteonecrosis of the jaw, in which the bone dies because of poor blood supply.

Patients who took Xgeva experienced deadly bone metastases 4.2 months later on average than those that took a placebo, Thousand Oaks, California-based Amgen found in a study published in November in The Lancet. Survival didn’t differ between the groups.

All of the men in Amgen’s study had tumors that did not respond well to hormone therapy, but had not yet spread beyond the prostate. While there are multiple drugs for both early and late-stage prostate cancer, Amgen argues “there is a gap in the treatment plan for those patients” enrolled in its study.

Michael Severino, Amgen’s vice president of research and development, said today that the company believes Xgeva does provide a clinically meaningful benefit because it delays the spread of cancer to the bone, which causes significant pain and other problems such as incontinence.

While the FDA staff does not openly recommend against the new use for the drug, they do quote from an editorial in the Lancet which said the company’s findings on Xgeva “do not support its broad use as a preventive agent for bone metastases in prostate cancer.”

ISI analyst Mark Schoenebaum said the FDA’s negative review was consistent with analyst expectations. “As was generally expected by us and much of the Street, the FDA is critical of the data, questioning the clinical meaningfulness of the primary endpoint,” Schoenebaum said. Even if the FDA ultimately approves the indication, Schoenebaum estimates modest U.S. sales of about $300 million. The FDA is expected to make its final decision by late April. Xgeva and Prolia, the osteoporosis formulation, had combined sales of $554 million in 2011, their first full year on the market. Amgen forecasts Xgeva sales of $3 billion to $4 billion in 2015.

“I would not be surprised if this doesn’t get approved,” said Bill Tanner, an analyst at Lazard Capital Markets in New York, in a telephone interview. “The only signal that they’ve seen is dubious clinical benefit.”

The agency is scheduled to make a decision by April 26.